司美格鲁肽治疗肥胖相关性心力衰竭合并 2 型糖尿病患者的效果。

Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes.

机构信息

From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.), the Diabetes Research Centre, University of Leicester, and the NIHR Leicester Biomedical Research Centre, Leicester (M.J.D.), and the Division of Cardiovascular Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester (F.Z.A.) - all in the United Kingdom; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); the Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Novo Nordisk, Søborg (G.K.H., D.V.M., M.B.T., T.J.J., K.L., M.L.L.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and the University of Alberta, Edmonton (J.A.E.) - both in Canada; the College of Health and Medicine, Australian National University, Canberra, ACT, Australia (W.A.); the Heart Failure Unit, Cardiology Department, Rabin Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (T.B.-G.); Max Super Speciality Hospital, Saket, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Östra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular - both in Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Socio Sanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); the Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.M.); the Medical University of Graz, Graz, Austria (D.V.L.); Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.); and the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.).

出版信息

N Engl J Med. 2024 Apr 18;390(15):1394-1407. doi: 10.1056/NEJMoa2313917. Epub 2024 Apr 6.

DOI:10.1056/NEJMoa2313917

PMID:38587233

Abstract

BACKGROUND

Obesity and type 2 diabetes are prevalent in patients with heart failure with preserved ejection fraction and are characterized by a high symptom burden. No approved therapies specifically target obesity-related heart failure with preserved ejection fraction in persons with type 2 diabetes.

METHODS

We randomly assigned patients who had heart failure with preserved ejection fraction, a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or more, and type 2 diabetes to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level.

RESULTS

A total of 616 participants underwent randomization. The mean change in the KCCQ-CSS was 13.7 points with semaglutide and 6.4 points with placebo (estimated difference, 7.3 points; 95% confidence interval [CI], 4.1 to 10.4; P<0.001), and the mean percentage change in body weight was -9.8% with semaglutide and -3.4% with placebo (estimated difference, -6.4 percentage points; 95% CI, -7.6 to -5.2; P<0.001). The results for the confirmatory secondary end points favored semaglutide over placebo (estimated between-group difference in change in 6-minute walk distance, 14.3 m [95% CI, 3.7 to 24.9; P = 0.008]; win ratio for hierarchical composite end point, 1.58 [95% CI, 1.29 to 1.94; P<0.001]; and estimated treatment ratio for change in CRP level, 0.67 [95% CI, 0.55 to 0.80; P<0.001]). Serious adverse events were reported in 55 participants (17.7%) in the semaglutide group and 88 (28.8%) in the placebo group.

CONCLUSIONS

Among patients with obesity-related heart failure with preserved ejection fraction and type 2 diabetes, semaglutide led to larger reductions in heart failure-related symptoms and physical limitations and greater weight loss than placebo at 1 year. (Funded by Novo Nordisk; STEP-HFpEF DM ClinicalTrials.gov number, NCT04916470.).

摘要

背景

肥胖和 2 型糖尿病在射血分数保留的心力衰竭患者中很常见，其特征是症状负担高。没有专门针对 2 型糖尿病患者肥胖相关射血分数保留型心力衰竭的批准疗法。

方法

我们随机分配了患有射血分数保留型心力衰竭、身体质量指数（体重以千克为单位除以身高的平方，即 BMI）为 30 或以上以及 2 型糖尿病的患者，接受每周一次的司美格鲁肽（2.4mg）或安慰剂治疗 52 周。主要终点是从基线开始的堪萨斯城心肌病问卷临床综合评分（KCCQ-CSS；评分范围为 0 到 100，分数越高表示症状和身体限制越少）和体重变化。确认性次要终点包括 6 分钟步行距离的变化；包括死亡、心力衰竭事件以及 KCCQ-CSS 和 6 分钟步行距离变化差异的分层综合终点；以及 C 反应蛋白（CRP）水平的变化。

结果

共有 616 名参与者接受了随机分组。司美格鲁肽组 KCCQ-CSS 的平均变化为 13.7 分，安慰剂组为 6.4 分（估计差值为 7.3 分；95%置信区间 [CI]，4.1 到 10.4；P<0.001），司美格鲁肽组体重的平均百分比变化为-9.8%，安慰剂组为-3.4%（估计差值为-6.4 个百分点；95%CI，-7.6 到-5.2；P<0.001）。确认性次要终点结果均有利于司美格鲁肽组优于安慰剂组（6 分钟步行距离变化的估计组间差异，14.3m[95%CI，3.7 到 24.9；P = 0.008]；分层综合终点的获胜率，1.58[95%CI，1.29 到 1.94；P<0.001]；以及 CRP 水平变化的估计治疗比值，0.67[95%CI，0.55 到 0.80；P<0.001]）。司美格鲁肽组有 55 名（17.7%）参与者和安慰剂组有 88 名（28.8%）参与者报告了严重不良事件。